In:
Infection and Immunity, American Society for Microbiology, Vol. 79, No. 3 ( 2011-03), p. 1086-1097
Abstract:
The protozoan pathogen responsible for the most severe form of human malaria, Plasmodium falciparum , replicates asexually in erythrocytes within a membrane-bound parasitophorous vacuole (PV). Following each round of intracellular growth, the PV membrane (PVM) and host cell membrane rupture to release infectious merozoites in a protease-dependent process called egress. Previous work has shown that, just prior to egress, an essential, subtilisin-like parasite protease called PfSUB1 is discharged into the PV lumen, where it directly cleaves a number of important merozoite surface and PV proteins. These include the essential merozoite surface protein complex MSP1/6/7 and members of a family of papain-like putative proteases called SERA (serine-rich antigen) that are implicated in egress. To determine whether PfSUB1 has additional, previously unrecognized substrates, we have performed a bioinformatic and proteomic analysis of the entire late asexual blood stage proteome of the parasite. Our results demonstrate that PfSUB1 is responsible for the proteolytic processing of a range of merozoite, PV, and PVM proteins, including the rhoptry protein RAP1 (rhoptry-associated protein 1) and the merozoite surface protein MSRP2 (MSP7-related protein-2). Our findings imply multiple roles for PfSUB1 in the parasite life cycle, further supporting the case for considering the protease as a potential new antimalarial drug target.
Type of Medium:
Online Resource
ISSN:
0019-9567
,
1098-5522
DOI:
10.1128/IAI.00902-10
Language:
English
Publisher:
American Society for Microbiology
Publication Date:
2011
detail.hit.zdb_id:
1483247-1
